The objective of the proposed research is to define and understand the role of humoral and cellular immune responses to specific Friend leukemia virus (FLV) polypeptides in the establishment and maintenance of dormant FLV infections in the DBA/2 mouse. We will use for this study a unique leukemia virus animal model in which we can stimulate active immune responses to FLV transformed cells in infected mice with a single injection of double stranded RNA from statolon, an extract of mycophage-infected Penicillium stoloniferum. This dsRNA converts a rapidly fatal leukemia virus infection to a dormant state with prolonged clinical remission. The anti-FLV leukemic cell activities of antibodies produced by mice have suppressed the development of FLV erythroleukemia will be studied both in vitro and in vivo using immunobiologic and molecular biologic techniques. A major goal will be to evaluate the role of antigenic modulation in the suppression of the FLV genome and the reestablishment of normal division in leukemic cells. We have found in preliminary experiments that inhibition of FLV erythroleukemic cell division occurs when they are placed in diffusion chambers incubated in dormant FLV infected mice. We will identify the host humoral factors that diffuse into the chambers to inhibit cell division and determine the status of the FLV genome in these non-dividing erythroleukemic cells. We will identify the components of the immune response and of the FLV polypeptides to which they are directed. We will search for antibodies that bind to virus induced polypeptides on the surface of spleen cells from mice with dormant FLV infections in order to determine the role of these antibodies in maintaining suppression of Friend virus erythroleukemia. Finally, the dsRNA from mycophage-infected Penicillium stoloniferum and other natural dsRNAs will be evaluated for immunostimulation and leukemosuppression.